title: Effect of inhibitors of mitochondrial respiratory chain complexes on the electromechanical activity in human myocardium.
abstract: THE AIM OF THE STUDY was to investigate the effect of inhibitors of mitochondrial respiratory chain complexes I, III, and IV on the electromechanical activity in human myocardium.
  
  
  METHODS
  The experiments were performed on the human myocardial strips obtained from patients with heart failure (NYHA class III or IV) using a conventional method of registration of myocardial electromechanical activity. Under the perfusion with physiological Tyrode solution (control), contraction force (P) was 0.94±0.12 mN (n=16), relaxation time (t₅₀) was 173.38±5.03 ms (n=15), action potential durations measured at 50% (AP₅₀) and 90% (AP₉₀) repolarization were 248.96±13.38 ms and 398.59±17.93 ms, respectively (n=13).
  
  
  RESULTS
  The inhibition of respiratory chain complex I by rotenone (3 × 10⁻⁵ M, the highest concentration applied) decreased contraction force of human myocardium to 48.99%±14.74% (n=3) (P<0.05); AP₅₀, to 81.34%±15.81%; and AP₉₀, to 87.28%±7.25% (n=3) (P>0.05) of control level, while relaxation time and resting tension remained almost unchanged. Antimycin A, an inhibitor of complex III, applied at the highest concentration (3 × 10⁻⁴ M) reduced P to 41.66%±8.8% (n=5) (P<0.001) and marginally increased t₅₀ and decreased the durations of AP. Anoxia (3 mM Na₂S₂O₄) that inhibits the activity of complex IV reduced the contraction force to 9.23%±3.56% (n=6) (P<0.001), AP₅₀ and AP₉₀ to 65.46%±9.95% and 71.07%±8.39% (n=5) (P<0.05) of control level, respectively; furthermore, the resting tension augmented (contracture developed).
  
  
  CONCLUSIONS
  Our results show that the inhibition of respiratory chain complex IV had the strongest inhibitory effect on the electromechanical activity of failing human myocardium.
authors.affiliation: Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Sukilėlių 17, 50161 Kaunas, Lithuania. membiof@med.kmu.lt
authors.forename: Vida
authors.initials: V
authors.lastname: Gendvilienė
authors.forename: Irma
authors.initials: I
authors.lastname: Martišienė
authors.forename: Danguolė
authors.initials: D
authors.lastname: Zablockaitė
authors.forename: Jonas
authors.initials: J
authors.lastname: Jurevičius
mesh_terms: D000368:Aged; D000968:Antimycin A / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D012402:Rotenone / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D012402:Rotenone; D000968:Antimycin A; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III